Clinically apparent muscle weakness and wasting occur commonly in hyperthyroidism. In order to assess the independent contributions to skeletal muscle weakness of both muscle wasting and qualitative changes in muscle contraction, we studied muscle strength and volume in a cohort of hyperthyroid patients. Data regarding the response of these paremters to normalization of serum thyroid hormone levels is currently available in 10 female patients (median age 39 yrs; range 17-92 yrs). Initial measurements were performed prior to treatment of hyperthyroidism. Repeat measurements were made within 6-9 months of the patients achieving a euthyroid state. Muscle strength was determined by Cybex II dynamometric assessment of knee flexion and extension. Lower extremity total muscle volume was measured by dual photon x-ray absorptiometry (Lunar DPX-L) and mid-thigh muscle cross sectional area was quantitated by computerized axial tomography. Treatment of hyperthyroidism and restoration of a euthyroid state resulted in mean increases of 10% in thigh muscle cross sectional area (range 1-32%) and 12% in total lower extremity muscle volume (range 1-31%). Mean thigh muscle strength increased by 57% (range 5-197%). Mean muscle efficiency, defined as the force of muscle contraction per unit of muscle volume (Nm/cm2) is increased by 48% (range 4-183%). This finding suggests that qualitative changes in the force of contraction result in decreased muscle efficiency. Responsible mechanisms remain to be fully elucidated.